The thermodynamic properties of small nonelectrolytes in salt solutions will be investigated, particularly those compounds whose study elucidates the mechanisms of interaction of salts with proteins. These studies will involve the determination of free energies and enthalpies of transfer of nonelectrolytes from water to salt solutions by electrochemical and calorimetric techniques. The effects of electrolytes on protein conformation will be investigated. Difference spectroscopy, calorimetry, and measurement of preferential hydration and differential metal ion binding will be employed. Estimates of the number of groups which change their environment during the course of protein denaturation will be made from these data. These results will be combined with the data obtained for the small model compounds to develop a quantitative thermodynamic interpretation of protein denaturation by electrolytes. The denaturation of proteins by heavy metal cations at low denaturant concentrations will be studied over a wide pH range. The aim will be to understand the mediation of these ions in conformational changes important in controlling biochemical mechanisms. BIBLIOGRAPHIC REFERENCES: E.R. Stimson and E.E. Schrier, Calorimetric Studies of the Interaction of Guanidinium Hydrochloride and Potassium Iodine with Model Amides in Aqueous Solution, 14, 509 (1975). Martha Y. Schrier, Peter J. Turner, and Eugene E. Schrier, Thermodynamic Quantities for the Transfer of Urea from Water to Aqueous Electrolyte Solutions, J. Phys. Chem., 79, 1391 (1975).